γ-Glutamyltransferase as a Novel Virulence Factor of Acinetobacter baumannii Inducing Alveolar Wall Destruction and Renal Damage in Systemic Disease

Abstract

A thorough understanding of Acinetobacter baumannii pathogenicity is the key to identifying novel drug targets. In the current study, we characterize the γ-glutamyltransferase enzyme (GGT) as a novel virulence factor. A GGT assay showed that the enzyme is secreted via the type II secretion system and results in higher extracellular activity for the hypervirulent AB5075 than the laboratory-adapted strain American Type Culture Collection 17978. Enzyme-linked immunosorbent assay revealed that the former secretes larger amounts of GGT, and a rifampicin messenger RNA stability study showed that one reason for this could be the longer AB5075 ggt transcript half-life. Infection models confirmed that GGT is required for the virulence of A. baumannii. Finally, we show that clinical isolates with significantly higher extracellular GGT activity resulted in more severe infections, and assay of immune response and tissue damage markers confirm this correlation. The current findings establish for the first time the role of the GGT in the pathogenicity of A. baumannii.

Keywords: A baumannii; MDR; secretion systems; systemic infection; virulence; γ-glutamyltransferase.